title: Biologic activity of a dinuclear Pd(II)-spermine complex toward human breast cancer.
abstract: A dinuclear palladium-based complex (Pd(2) -Spm) was synthesized and compared with cisplatin (cDDP) on two different human breast cancer cell lines (MCF-7 and MDA-MB-231) as well as toward an untransformed cell line (BJ fibroblasts). The results obtained show that Pd(2) -Spm is more effective against the estrogen receptors [ER(-)] cell line MDA-MB-231, while cDDP displayed better results for the ER(+) MCF-7 cell line. It was shown that, like cDDP, Pd(2) -Spm triggers phosphorylation of H2AX, indicating that this compound damages DNA. Apart from DNA, Pd(2) -Spm also targets the cytoskeleton having a greater impact on cell morphology than cDDP. Pd(2) -Spm and cDDP have opposite antiproliferative activities in the presence of the PI3K inhibitor wortmannin. Furthermore, Pd(2) -Spm at an optimized concentration displays a rapid antiproliferative effect as opposed to cDDP, which seems to have a slower kinetics. The results point to a distinct mechanism of action for each of these complexes, which may explain their synergistic action when coadministrated.
authors.affiliation: Química-Física Molecular, Departamento de Química, FCTUC, Universidade de Coimbra, Portugal. sonia.mfiuza@gmail.com
authors.forename: Sónia M
authors.initials: SM
authors.lastname: Fiuza
authors.forename: Jon
authors.initials: J
authors.lastname: Holy
authors.forename: Luis A E
authors.initials: LA
authors.lastname: Batista de Carvalho
authors.forename: Maria P M
authors.initials: MP
authors.lastname: Marques
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D005260:Female; D006801:Humans; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D010165:Palladium / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013096:Spermine / Q000737:chemistry / Q000494:pharmacology*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D047428:Protein Kinase Inhibitors; D013096:Spermine; D010165:Palladium; D000077191:Wortmannin